TY - JOUR
T1 - C1q is increased in cerebrospinal fluid-derived extracellular vesicles in Alzheimer's disease
T2 - A multi-cohort proteomics and immuno-assay validation study
AU - Chatterjee, Madhurima
AU - Özdemir, Selcuk
AU - Kunadt, Marcel
AU - Koel-Simmelink, Marleen
AU - Boiten, Walter
AU - Piepkorn, Lars
AU - Pham, Thang V.
AU - Chiasserini, Davide
AU - Piersma, Sander R.
AU - Knol, Jaco C.
AU - Möbius, Wiebke
AU - Mollenhauer, Brit
AU - van der Flier, Wiesje M.
AU - Jimenez, Connie R.
AU - Teunissen, Charlotte E.
AU - Jahn, Olaf
AU - Schneider, Anja
N1 - Funding Information:
Charlotte E. Teunissen: Received grants from the European Commission, the Dutch Research Council (ZonMW), Association of Frontotemporal Dementia/Alzheimer's Drug Discovery Foundation, The Weston Brain Institute, Alzheimer Netherlands.
Funding Information:
There was no project specific funding from any grant agency.
Funding Information:
Brit Mollenhauer: Received research funding from the Deutsche Forschungsgemeinschaft (DFG), EU (Horizon2020), Parkinson Fonds Deutschland, Deutsche Parkinson Vereinigung, and the Michael J. Fox Foundation for Parkinson's Research.
Funding Information:
Wiesje M. van der Flier: WF received research funding from ZonMW, NWO, EU‐FP7, EU‐JPND, Alzheimer Nederland, CardioVascular Onderzoek Nederland, Health∼Holland, Topsector Life Sciences & Health, stichting Dioraphte, Gieskes‐Strijbis fonds, stichting Equilibrio, Pasman stichting, Biogen MA Inc, Boehringer Ingelheim, Life‐MI, AVID, Roche BV, Fujifilm, Combinostics.
Funding Information:
Wiesje M. van der Flier employment by Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, the Netherlands. WF is consultant to Oxford Health Policy Forum CIC, Roche, and Biogen MA Inc. WF participated in an advisory board of Biogen MA Inc and Roche and received funding from Biogen MA Inc, Boehringer Ingelheim, Life‐MI, AVID, Roche BV, Fujifilm, Combinostics..
Funding Information:
Madhurima Chatterjee: Recipient of funding from Deutsche Demenzhilfe and Manfred‐Strohscheer‐Stiftung.
Publisher Copyright:
© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
PY - 2023
Y1 - 2023
N2 - Introduction: Extracellular vesicles (EVs) may propagate and modulate Alzheimer's disease (AD) pathology. We aimed to comprehensively characterize the proteome of cerebrospinal fluid (CSF) EVs to identify proteins and pathways altered in AD. Methods: CSF EVs were isolated by ultracentrifugation (Cohort 1) or Vn96 peptide (Cohort 2) from non-neurodegenerative controls (n = 15, 16) and AD patients (n = 22, 20, respectively). EVs were subjected to untargeted quantitative mass spectrometry-based proteomics. Results were validated by enzyme-linked immunosorbent assay (ELISA) in Cohorts 3 and 4, consisting of controls (n = 16, n = 43, (Cohort3, Cohort4)), and patients with AD (n = 24, n = 100). Results: We found > 30 differentially expressed proteins in AD CSF EVs involved in immune-regulation. Increase of C1q levels in AD compared to non-demented controls was validated by ELISA (∼ 1.5 fold, p (Cohort 3) = 0.03, p (Cohort 4) = 0.005). Discussion: EVs may be utilized as a potential biomarker and may play a so far unprecedented role in immune-regulation in AD.
AB - Introduction: Extracellular vesicles (EVs) may propagate and modulate Alzheimer's disease (AD) pathology. We aimed to comprehensively characterize the proteome of cerebrospinal fluid (CSF) EVs to identify proteins and pathways altered in AD. Methods: CSF EVs were isolated by ultracentrifugation (Cohort 1) or Vn96 peptide (Cohort 2) from non-neurodegenerative controls (n = 15, 16) and AD patients (n = 22, 20, respectively). EVs were subjected to untargeted quantitative mass spectrometry-based proteomics. Results were validated by enzyme-linked immunosorbent assay (ELISA) in Cohorts 3 and 4, consisting of controls (n = 16, n = 43, (Cohort3, Cohort4)), and patients with AD (n = 24, n = 100). Results: We found > 30 differentially expressed proteins in AD CSF EVs involved in immune-regulation. Increase of C1q levels in AD compared to non-demented controls was validated by ELISA (∼ 1.5 fold, p (Cohort 3) = 0.03, p (Cohort 4) = 0.005). Discussion: EVs may be utilized as a potential biomarker and may play a so far unprecedented role in immune-regulation in AD.
KW - Alzheimer's disease (AD)
KW - biomarker
KW - cerebrospinal fluid (CSF)
KW - complement
KW - extracellular vesicles
KW - immune system
KW - mild cognitive impairment (MCI)
KW - proteomics
UR - http://www.scopus.com/inward/record.url?scp=85152066008&partnerID=8YFLogxK
U2 - 10.1002/alz.13066
DO - 10.1002/alz.13066
M3 - Article
C2 - 37023079
SN - 1552-5260
JO - Alzheimers & Dementia
JF - Alzheimers & Dementia
ER -